Epilepsy and Viral Infections

Theodore, William H.

doi:10.5698/1535-7511-14.s2.35

Cited by 18 publications

(17 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In response to viral infections, increased levels of cytokines, chemokines and other inflammatory mediators can directly damage mitochondria, resulting in oxidative stress. Herpes simplex virus (HSV) and Japanese encephalitis virus (JEV) are among the most common viruses which cause encephalitis and are both associated with acute seizures in patients (Theodore, 2014). Acute and chronic HSV-1 infection in mice results in inflammation and oxidative damage to the neurons and non-neuronal cells in the brain (Valyi-Nagy & Dermody, 2005).…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress in murine Theiler's virus-induced temporal lobe epilepsy

Bhuyan

Patel

Wilcox

et al. 2015

Experimental Neurology

View full text Add to dashboard Cite

Temporal lobe epilepsy (TLE) is the most common form of acquired epilepsy that can be caused by several inciting events including viral infections. However, one-third of TLE patients are pharmacoresistant to current antiepileptic drugs and therefore, there is an urgent need to develop antiepileptogenic therapies that prevent the development of the disease. Oxidative stress and redox alterations have recently been recognized as important etiological factors contributing to seizure-induced neuronal damage. The goal of this study was to determine if oxidative stress occurs in the TMEV (Theiler’s murine encephalomyelitis virus) model of temporal lobe epilepsy (TLE). C57Bl/6 mice were injected with TMEV or with PBS intracortically and observed for acute seizures. At various time points after TMEV injection, hippocampi were analyzed for levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and 3-nitrotyrosine (3NT). Mice infected with TMEV displayed behavioral seizures between days 3 and 7 days post-infection (dpi). The intensity of seizures increased over time with most of the seizures being a stage 4 or 5 on the Racine scale at 6 days p.i. Mice exhibiting at least one seizure during the observation period were utilized for the biochemical analyses. The levels of GSH were significantly depleted in TMEV infected mice at 3, 4 and 14 days p.i. with a concomitant increase in GSSH levels as well as an impairment of the redox status. Additionally, there was a substantial increase in 3NT levels in TMEV infected mice at these time points. These redox changes correlated with the occurrence of acute seizures in this model. Interestingly, we did not see changes in any of the indices in the cerebellum of TMEV-infected mice at 3 dpi indicating that these alterations are localized to the hippocampus and perhaps other limbic regions. This is the first study to demonstrate the occurrence of oxidative stress in the TMEV model of infection-induced TLE. The redox alterations were observed at time points coinciding with the appearance of acute behavioral seizures suggesting that these changes might be a consequence of seizure activity. Our results support the hypothesis that redox changes correlate with seizure activity in acquired epilepsies, regardless of the inciting insults, and suggest oxidative stress as a potential therapeutic target for their treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Oxidative stress in murine Theiler's virus-induced temporal lobe epilepsy

Bhuyan

Patel

Wilcox

et al. 2015

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…An emerging hypothesis is that various brain insults, including viral infections, can contribute to epileptogenesis by inducing a cascade of chronic central nervous system (CNS) inflammatory processes and increased blood-brain barrier permeability, leading to enhanced neuronal excitability. 3,4 Previous studies highlighted the role of glial cells (astrocytes and microglia) and neurons in production of inflammatory cytokines. 5 Preclinical studies showed that interleukin (IL)1β…”

Section: Steven Jacobsonmentioning

confidence: 99%

Differential Activation of Neuroinflammatory Pathways in Children with Seizures: A Cross-Sectional Study

Bartolini

Moran

Norato

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Experimental and clinical findings suggest a crucial role of inflammation in epileptogenesis. We aimed to analyze levels of inflammatory cytokines in plasma and saliva from children with acute seizures and healthy controls and measure their associations with HHV6 and EBV infection. Methods: We analyzed plasma from 36 children within 24 hours of acute seizures (cases) and 43 healthy controls and saliva from 44 cases and 44 controls with a multiplex immunoassay. Saliva from all controls and 65 cases and blood from 26 controls and 35 cases were also analyzed by ddPCR for viral DNA. Statistical analysis included Wilcoxon Rank Sum test, Fisher’s exact test, ANOVA and Spearman correlation. Results: Compared to controls, children with breakthrough seizures (n=18) had higher levels of CCL11 (p<0.001), CCL26 (p<0.001), IL-8 (p=0.03), CCL4 (p=0.02) in plasma. Children with new onset seizures (n=13) showed higher levels of CCL11 (p=0.05) and IL-6 (p=0.01). Patients with febrile seizures (n=5) had higher levels of IFNg (p<0.001), IL-6 (p<0.001), IL-10 (p<0.001), CXCL10 (p=0.001). CCL11 was higher with 3 or more seizures (p=0.01), seizures longer than 10 minutes (p=0.001) and when EEG showed focal slowing (p=0.02). In saliva, febrile seizures had higher levels of IL-1β (n=7, p=0.04) and new onset seizures had higher IL-6 (n=15, p=0.02). Plasma and saliva cytokine levels did not show correlation. Frequency of HHV-6 and EBV detection was similar across seizure types and not different than controls. We found no correlation between viral load and cytokine levels Conclusions: We showed differential activation of neuroinflammatory pathways in plasma from different seizure etiologies compared to controls, unrelated to HHV-6 infection.

show abstract

“…Viral encephalitis is often associated with seizures and results in an increased risk of developing chronic epilepsy after recovery from infection [2,7,8,27]. The magnitude of the increased risk of chronic epilepsy is dependent on the occurrence of seizures during the acute infection.…”

Section: Introductionmentioning

confidence: 99%

“…The magnitude of the increased risk of chronic epilepsy is dependent on the occurrence of seizures during the acute infection. The 20-year risk of developing epilepsy is 22% in patients that suffered seizures during infection and 10% in patients that exhibited no seizures [2,27]. Viral encephalitis can cause mesial temporal sclerosis [27] and results in epilepsies that are particularly difficult to treat with traditional pharmacological therapies [18].…”

Section: Introductionmentioning

confidence: 99%

“…The 20-year risk of developing epilepsy is 22% in patients that suffered seizures during infection and 10% in patients that exhibited no seizures [2,27]. Viral encephalitis can cause mesial temporal sclerosis [27] and results in epilepsies that are particularly difficult to treat with traditional pharmacological therapies [18]. In order to better understand and to explore novel pharmacological therapies for virus-induced epilepsies, our laboratory uses the Theiler’s murine encephalomyelitis virus (TMEV) C57Bl/6 mouse model [15,22,24].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Decrease in CA3 inhibitory network activity during Theiler’s virus encephalitis

Smeal

Fujinami

White

et al. 2015

Neuroscience Letters

View full text Add to dashboard Cite

Viral infections of the central nervous system are often associated with seizures, and while patients usually recover from the infection and the seizures cease, there is an increased lifetime incidence of epilepsy. These viral infections can result in mesial temporal sclerosis, and, subsequently, a type of epilepsy that is difficult to treat. In previous work, we have shown that Theiler’s murine encephalomyelitis virus (TMEV) infections in C57B/6 mice, an animal model of virus-induced epilepsy, results in changes in excitatory currents of CA3 neurons both during the acute infection and two months later, at a time when seizure thresholds are reduced and when spontaneous seizures can occur. The changes in the excitatory system differ at these two time points, suggesting different mechanisms for seizure generation. In the present paper, we examine GABAergic mediated inhibition in CA3 pyramidal cells at these two time points following TMEV infection. We found that amplitudes of sIPSCs and mIPSCs were reduced during the acute infection, but recovered at the two-month time point. These observations are consistent with previous measurements of excitatory currents suggesting different mechanisms of seizure generation during the acute infection and during chronic epilepsy.

show abstract

Epilepsy and Viral Infections

Cited by 18 publications

References 46 publications

Oxidative stress in murine Theiler's virus-induced temporal lobe epilepsy

Oxidative stress in murine Theiler's virus-induced temporal lobe epilepsy

Differential Activation of Neuroinflammatory Pathways in Children with Seizures: A Cross-Sectional Study

Decrease in CA3 inhibitory network activity during Theiler’s virus encephalitis

Contact Info

Product

Resources

About